Inflammation is the foundation for cancer and degenerative/autoimmune diseases. Small changes in diet and exercise, e.g. omega-3 oils, vitamin D, low starch, and maintaining muscle mass, can dramatically alter predisposition to disease and aging, and minimize the negative impact of genetic risks. Based on my experience in biological research, I am trying to explain how the anti-inflammatory diet and lifestyle combat disease. 190 more articles at http://coolinginflammation.blogspot.com

Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:

Thursday, January 29, 2015

A healthy, functional gut microbiota (bacteria and fungi) supplies all of the vitamins needed, stimulates the development of a balanced immune system and promotes vitality.If you feed and maintain the diversity of the pounds of bacteria in your gut, you will be healthy.If you listen to the medical and food industries, you will be sick, i.e. a good patient/consumer.

Supplements Compensate for Deficiencies/Sickness

The key to this discussion is the functions of the healthy communities of bacteria and fungi called the gut microbiota. These pounds of bacteria produce all of the vitamins that your body needs, and spiking your diet with multivitamins may disrupt your microbiota, because vitamins are actually the chemical signals used for communications between bacteria in biofilms. Numerous studies have shown that daily multivitamins are not beneficial, so if you see extra vitamins on the ingredients label, try some whole foods instead. If, however, you have been exposed to antibiotics or other medications, since most have potent antibiotic activities, then your gut bacteria may not be producing vitamins normally, and you may need to supplement. Vitamin deficiencies are a symptom of gut dysbiosis, damaged gut microbiota.

Vitamin D is a Steroid Hormone Produced from Cholesterol in Skin by Sunlight

Most people know that sunlight striking skin produces vitamin D, but they still think that they can get a significant amount of vitamin D from their diet. The confusion comes from the fact that vitamin D is a major hormone that influences many body systems including bone production and immunity. So in the absence of skin production of vitamin D, the low amounts added to milk are sufficient to prevent deficiency/rickets. However, chronic inflammation can block solar production of vitamin D, so that even individuals near the equator and basking daily still remain deficient. Vitamin D deficiency may also, insidiously, be a major source of chronic inflammation. Thus, most individuals treated for deficiency with supplemental vitamin D3, do not reach high enough levels to suppress chronic inflammation and restart solar production, so they remain deficient. Chronic inflammation is a symptom of vitamin D deficiency.

Bowel Cleanses Damage Gut Microbiota

The bowels are a long tubelike conveyance and it takes food about a day to travel from table to toilet. In the colon, all of the plant polysaccharide fibers remaining after removal of sugar, starch, fat and protein, are digested by enzymes of the microbiota and converted into more bacteria and short chain fatty acids that feed the colon tissue. There is nothing toxic left behind in the colon. Protein from meat is readily digested in the stomach and the first part of the small intestines. Plant materials cannot be digested without the help of a complex array of hundreds of enzymes produced by gut bacteria. Food intolerances are caused by the loss of particular bacterial species needed for complete digestion of one type of plant fiber. The bacteria form the stools, and insufficient healthy bowel bacteria, normally fed by the fiber, is the cause of constipation. Clearly, flushing out bacteria with a "cleanse" is unhealthy and counterproductive. There is nothing in the colon but gut bacteria and fiber to feed the bacteria. Those bacteria are needed for vitamin production, normal development of the immune system and normal stools. A cleanse merely removes healthy gut bacteria and leads to constipation or replacement by pathogens.

Diverse and complex plant polysaccharides, e.g. pectin, arabinogalactan, various glucans and fructans, are systematically digested by hundreds of different bacterial enzymes of the healthy gut microbiota. The sugars that result are eventually converted into short chain fatty acids, such as butyrate, that feed the cells lining the colon. The plant polysaccharides that feed gut bacteria are called prebiotics. Unfortunately, prebiotics are removed during food processing to enhance ease of preparation and palatability. The result of decreased dietary prebiotics is selective starvation and removal of bacterial species needed for the development of the immune system, and autoimmune diseases.

Most Medicines Have Substantial Antibiotic Activity and Damage Gut Microbiota

It is not surprising that antibiotics damage the bacteria in the gut. What most people don’t realize is that most pharmaceuticals/medicines are developed from the natural antibiotics of plants, phytoalexins. Numerous recent studies have demonstrated most common medicines, e.g. statins, NSAID, antidepressants, etc. have substantial antibiotic activity and damage gut bacteria. Surgeons commonly suggest that patients eat yogurt to help repair their gut micro biomes after operations and antibiotics, but they don’t tell them how to fix their gut and immune system as they take medications for the rest of their lives. The permanently damaged gut just causes further deterioration of the immune system and health.

Resistance to essential oil antibiotic activity is slower, because of simultaneous use of multiple antibiotics.

Obesity is a Symptom of Antibiotic Damage to Gut Microbiome

Antibiotics make meat fatter

We may enjoy a fat marbled steak, but the corn and antibiotics used to produce that mouth-watering plate of satiety, is not so healthy. Corn and antibiotics make that meat on the hoof fit for human consumption, but the cattle are quickly dying and the fat marbling is a symptom of cattle metabolic syndrome. The corn and antibiotics disrupt the bovine gut microbiota and alter energy flow. The result is prime beef.

As It Is with Cattle, so It Is with Middle Americans

General descriptions of Americans with metabolic syndrome and steers ready for the abattoir are similar. That should not be surprising, because both are caused by damaged gut microbiota and consequences of metabolic syndrome. Americans routinely damage their gut microbiota with antibiotics (processed food, etc.) and the major symptoms of the resulting gut dysbiosis are chronic inflammation, depression, autoimmune diseases, obesity and metabolic syndrome. Repairing gut microbiota reverses all of these symptoms.

But Essential Oils Are Just Natural Antibiotics

Essential oils are natural antibiotics

Is it better to use essential oils than medical antibiotics to fatten cattle or treat Lyme disease or hospital infections such as C. diff.? Most pharmaceuticals were derived from plants or fungi and were originally used to kill microorganisms, i.e. they were natural antibiotics. We call these phytochemicals by a variety of names, e.g. antioxidants or essential oils, but they are more appropriately called phytoalexins, all natural, all plant, all toxic antibiotics. It is entertaining that essential oils have had so many different traditional and pharmaceutical uses, and yet they have always been experienced by microorganisms (and our livers) as simply toxic. Essential oils do have the significant advantage of being a mixture of antibiotics and might be very useful where pharmaceutical antibiotics have problems. The toxicity of essential oils, especially toward gut bacteria, should not be ignored.

Resistance to Essential Oils as Antibiotics

Antibiotic resistance develops in sewage

I previously kept track of laboratory strains of bacteria by simply exposing large numbers of the bacteria to an antibiotic and selecting for the rare individual that had already spontaneous mutated (DNA replication error of one in a million). We could then use the new drug resistant strain in experiments and identify it by its resistance. The same thing happens to your gut bacteria with an overnight exposure to an antibiotic. And of course it also occurs immediately in livestock exposed to antibiotics or in sewage plants where tons of antibiotics and gut bacteria are mixed. Resistance to each of the chemicals in an essential oil also would rapidly occur, if bacteria were exposed to each alone and in a toxic concentration. This is repeatedly observed, since commonly used drugs are just individual components of essential oils that have been produced in large amounts in pills and marketed based on their predominant physiological activity, rather than just another antibiotic. Thus, resistance to a statin or Metformin, as antibiotics, could be easily observed (even on multiple drug resistance plasmids), but is just ignored.

Essential Oils Are just Mixtures of Natural Antibiotics

Statins from fungal antibiotics

The impact of essential oils on gut microbiota is unpredictable, because the composition of essential oils is highly dynamic and so are gut microbiota. Each component of an essential oil has a different spectrum of toxicities to hundreds of different target proteins to each of the hundreds of different species of bacteria in the human gut. Ingested essential oils are modified by the detox enzymes of the intestine and liver. The modified phytochemicals have different toxicities and act as additional antibiotics. Mixtures of antibiotics, as in essential oils, less likely to select for resistance than individual antibiotics, but an antibiotic is still just an antibiotic, regardless of whether it is straight from the plant or via a pharmaceutical salesman.

Common Medicines Are the Source of Superbugs

Common meds are antibiotics

Doctors with prescription pads and steers eating antibiotics are blamed, I think unjustly, for the crisis of antibiotic resistance. The real culprit is you taking NSAIDs, statins, proton pump inhibitors, antidepressants and other common medicines. Since they are all developed from plant antibiotics, they are still antibiotics, and they still select for antibiotic resistance. It is important to remember that pharmaceuticals are repurposed natural antibiotics from plants. The answer to the superbugs that are resistant to all of the common antibiotics is to dramatically reduce the use of all pharmaceuticals. The initial goal should be a 90% reduction. Costly pharmaceutical chemicals could be replaced with preventive diets and less disruptive manipulations of gut microbiota, e.g. ingestion of capsules containing freeze-dried gut flora. This more gentle approach to health care would also provide huge cost savings, as well as vastly improving health.

Monday, January 19, 2015

The year 2014 began with my posts on damage to the gut microbiotacaused by antibiotics, processed foods and excess hygiene.I lamented the inadequacy of information from the media on damage/repair of the gut bacteria and highlighted medical myths with a post on some of Dr. Oz’s own ills that are self-inflicted by his diet and hygiene recommendations.I also started to discuss how to cure autoimmune diseases by repairing damaged gut flora and by avoiding the antibiotic activity present in many common drugs.

With my 200th post in March, I summarized my thoughts on the causes and cures of common diseases in a series of diagrams on:

I illustrated the relationships among diet, inflammation and diseases mediated by gut flora that I have discussed, since I started my blog in 2008. Now after a couple of hundred articles and more than two million visits to my blog, I think that I am starting to grasp some of the major issues that cause inflammatory diseases. The cures also now seem obvious.

Antibiotics Contribute to Autoimmune Diseases

Some species of gut bacteria are needed for the development of the aggressive half of the immune system and other species are needed for the suppressive half. Thus, starving or poisoning gut flora leads to immune system problems and diseases. Antibiotics are a quick way of crippling the immune system. It seems that the aggressive part of the immune system is less fragile, because in most cases antibiotic treatments produce autoimmune disease due to loss of bacteria that are needed for development of immune cells that block the aggressive half of the immune system from attacking innocuous cells of the body or environment, i.e. antibiotics usually trigger deficient tolerance, and autoimmunity.

Feed the Gut Microbiome for a Healthy Immune System

Diet provides food for the body and flora. Protein and fat are the macronutrients needed for the body, while the gut microbiota lives off of plant polysaccharides (except starch) that pass through the small intestines undigested into the colon. The hundreds of plant polysaccharides are hydrolyzed by hundreds of enzymes made by gut flora and produce short chain fatty acids, e.g. acetate and butyrate, that feed colon cells. Food processing systematically removes polysaccharides that feed gut flora and compromises the components of the immune system dependent on those bacteria.

Repairing the Gut Microbiome by Eating the Missing Bacteria

It is easier to see that eating a diet that lacks food for the gut microbiota will be a problem, than it is to figure out where to find replacements for lost species of gut bacteria. The only way that bacteria get into the gut is down the throat. To repair a damaged gut microbiota requires both changing diet and introducing the missing types of bacteria by eating them. Eating dairy probiotics and fermented vegetables can provide a quick, but only temporary fix. Most of the needed bacteria are more common in soil than in food.

Phytochemicals Are First and Foremost Antibiotics

I was shocked that my background in phytochemicals didn’t lead more directly to a major culprit causing modern diseases. The gut microbiota is clearly a major factor in health and sickness. Antibiotics that kill bacteria, damage the gut microbiota. It is also unsurprising that processing food to reduce soluble fiber, damages gut flora, by systematically depriving gut bacteria of their major source of food. The proliferation of antimicrobial products also damages the gut flora. What I missed in this onslaught of modern lifestyles on the gut microbiota, was the major player in antibiotic resistance — phytochemicals are natural antibiotics.

I Missed the Antibiotic Activity of Common Medicines

I studied phytochemicals and wrote research articles on their toxic, antibiotic activities, but everyone else was merchandizing phytochemicals as antioxidants, essential oils and superfoods. This is a major conceptual problem. Our bodies expend a significant fraction of our energy resources to detoxicify phytochemicals and human cultures have elaborate rituals to avoid phytochemicals and domesticate plants by breeding for the least toxic. What I missed was the implication that the pharmaceutical industry was repurposing toxic, antibiotic phytochemicals as medicines and then skipping the "antibiotic" label.

Unlabelled Antibiotic Drugs Cause the Rise of Superbugs

Overuse of antibiotics is a problem, because it damages the gut microbiome and contributes to the modern increase in autoimmunity. Food processing is another culprit and so is the mania for hyperhygiene and the demonization of bacteria. Unfortunately, the major culprit in the development of multiple antibiotic resistant superbugs is the tons of commonly used pharmaceuticals that systematically attack gut bacteria, but are not labelled as antibiotics. Most modern drugs were developed from phytochemicals and were initially used in plants to kill bacteria and fungi, i.e. phytoalexins. Pharmaceutical companies acknowledge the antibiotic activities of common drugs, by sponsoring research conferences to develop existing drugs as new classes of antibiotics for treatment of superbugs.

Friday, January 2, 2015

'Tis the season to discuss phytochemicals.Plants produce a vast array of organic chemicals starting from molecules produced by all organisms, including humans.Essentially all of these phytochemicals are potent adaptations to kill.Phytochemicals kill plant pathogens, bacteria and fungi, as well as insects.Thus, the natural, plant extracts that humans use for flavor enhancers (herbs, spices, and teas), fragrances, recreational/medicinal mind and attitude modifiers (alkaloids, psychopharmaceuticals, etc.), herbal medicines, etc. are present in plants, first and foremost, as antibiotics and insecticides.Humans have evolved to taste (bitter) and smell phytochemicals to avoid their toxicity, and have adapted culturally to exploit the impact of phytochemicals on body and mind.In this seasonal post, I focus on the terpenoids in Frankincense and Myrrh, to explore how plant biochemistry contributed to the gifts of the Magi.

It All Starts with Central Metabolism

Phytochemicals are complicated plant chemicals that are produced by a series of enzyme-controlled reactions (Central Metabolism) from the array of chemicals used by plants to convert photosynthetic carbohydrates (fructose and glucose) into the molecules (sugars, amino acids, fatty acids, nucleic acids) used to make the macromolecules of cells (polysaccharides, proteins, fats, DNA/RNA). Alkaloids and phenolics, e.g. phytoalexins, are made from amino acids (phenylalanine) and terpenoids are made from fatty acids (acetyl CoA/Mevalonate) or other intermediates in glycolysis. Thus, central metabolism that converts glucose/fructose into pyruvate and the acetyl CoA (see mevalonate pathway left) of mitochondrial fatty acid metabolism, is further converted into amino acids and plant secondary compounds, phytochemicals. I am going to talk mainly about terpenoids in Frankincense (triterpenoid Boswellic acids) and Myrrh, and many related molecules (steroids) also produced by humans.

The major thesis here is that carbon dioxide is converted by photosynthesis into either sugars used to build the cell wall polysaccharides (soluble fiber) or larger toxic defensive chemicals, e.g. phytoalexins, resins, essential oils or lignin. Phytoalexins, e.g. the natural antibiotic resveratrol in wine, are made from phenylalanine along the same biochemical pathway used to produce lignin. Glyphosate, the herbicide, kills by blocking this unique plant pathway. Essential oils and resins are another group of natural antibiotics produced by converting acetyl CoA into a five carbon unit, IPP, which is then linked into larger and larger (10, 15, 20 carbons) molecules, terpenoids, that can rearrange into multiple ring structures. Only the smallest chemicals in the series evaporate to provide identifiable smells, e.g. Frankincense and Myrrh, while larger forms, e.g. cholesterol or testosterone in animals, are odorless solids.

Acetyl CoA to IPP

IPP

For those who enjoy the beauty of biochemistry: The most abundant enzyme on earth is RibisCo (ribulose bisphosphate carboxylase), the plant enzyme that combines carbon dioxide from air with a five-carbon phosphorylated sugar, ribulose bisphosphate, to produce two, three-carbon intermediates of glycolysis that can be converted into glucose or into acetyl CoA, the starting chemical for fatty acids, the mitochondrial TCA cycle, or via mevalonic acid to isopentanyl pyrophosphate (IPP), the building block for terpenoid synthesis.

In brief: Photosynthesis uses the energy from sunlight to convert carbon dioxide into sugars (glucose and fructose). Those sugars can be converted into a five-carbon, molecular building block for terpenoids, IPP. IPP molecules can then be linked together to make increasingly longer chains and those chains can be ultimately twisted into rings to make resins in plants and steroids in humans.

Terpenoid synthesis begins with IPP, which has five carbons in a branched chain and has a pair of phosphates, pyrophosphate that provide the energy to form chains of 5, 10, 15, etc. In plants, molecules of each of the incremental lengths are produced together and additional enzymes in different species of plants result in mixtures of molecules with different rings and functional groups. The smaller molecules evaporate more readily, so that mixtures are extruded from damaged trees as oils and gradually form resins as the remaining larger molecules predominate and solidify.

Shark Livers and the Horn of Africa

IPP with five carbons, an isoprene, is used to make GPP with ten, a monoterpene. Common monoterpenes are geranol and limonene that make the characteristic odors of geraniums and lemons. Sesquiterpenoids (15 carbons made from three IPPs) include the fragrance of patchouli. Diterpenes, such as sweet steviol, have twenty carbons, which can be chemically twisted into the chemicals that predominate in Myrrh resin, the Balm of Gileade. The triterpenes with 30 carbons can be rearranged with five rings to form steroids, such as cholesterol in animals or Frankincense. Linear squalene, is the major component in shark liver oil and provides the same function as a swim bladder in a boney fish.

Essential Oils Are Mixtures of Distilled Terpenoid and Phenylpropanoid Phytoalexins

Boswellic Acid

Phytoalexins and terpenoids have evolved as plant defenses against bacteria, fungi and insects, and they are toxic, because they interact aggressively with proteins through their chemical ring structures that are hydrophobic. These ring structures make the smaller versions volatile and soluble in organic solvents. Many of these chemicals have properties similar to petroleum products and may be used as solvents themselves, e.g. paint strippers or thinner. Steam distillation of plants produces mixtures of phytoalexins and terpenoids commonly called essential oils, which contain the volatile components “essential” for the odor identity of a plant.

Statins Block Cholesterol Synthesis

Statins were identified among a group of fungal antibiotics for their ability to block an early enzyme (marked in the mevalonate pathway above) in the production of cholesterol. The toxic side effects of statins derive from wholesale disruption of all of the essential pathways (everything below the inhibited enzyme) that are related to cholesterol, such as blood heme A found in hemoglobin, and ubiquinone (CoQ) found in mitochondrial electron transport and needed to reduce oxidative stress and glucose intolerance. Thus, for these examples, statins would contribute to anemia and type II diabetes/metabolic syndrome. The side effects are not surprising, since statins are fungal antibiotics that target pathways common to bacteria and human mitochondria. It is also not surprising that statins have unpredictable impacts on gut flora and the immune system.

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About Me

I grew up in San Diego and did my PhD in Molecular, Cellular and Developmental Biology (U. Colo. Boulder). I subsequently held postdoctoral research positions at the Swedish Forest Products Research Laboratories, Stockholm, U. Missouri -Colombia and Kansas State U. I was an assistant professor in the Cell and Developmental Biology Department at Harvard University, and an associate professor and Director of the Genetic Engineering Program at Cedar Crest College in Allentown, PA. I joined the faculty at the College of Idaho in 1991 and in 1997-98 I spent a six-month sabbatical at the National University of Singapore. Most recently I have focused on the role of heparin in inflammation and disease.